Scaffolds are porous structures into which cells may be incorporated. They are usually made up of biocompatible, degradable materials and are added to tissue to guide the organization, growth and differentiation of cells in the process of forming functional tissue. The materials used can be either of natural or synthetic origin.
Poly(L-lactide) (PLLA), poly(D/L-lactide) (PDLLA) and poly(lactide-co-glycolide) (PLGA) have been known for a long time as degradable implant materials, and they are all FDA-approved for this purpose. They have been used as scaffolds for bone, cartilage, liver, skin, urethra, intestines, tendon and cardiovascular tissues.
A typical example of one of these applications is that the polymer is made into a porous structure, often by solvent casting/particle leaching. The structure is then pre-wetted with ethanol, and washed successively with water. This step is necessary because these polymers are hydrophobic, and an attempt to wet them directly with water fails. The wet structure is then seeded with cells and grown in a bioreactor before implantation.
Copolymers of polyethers and polyesters are also known. These are usually not used as scaffolds, as PEG-containing (polyethylene glycol) polymers are known to resist adhesion of cells and proteins. This class of polymers are used as carriers in drug delivery, where the high hydrophilicity and fouling-resistance of the polyether part is useful.
PLGA and copolymers of PEG and PLGA are known to have good biocompatibility in that they are non-toxic for cells and do not invoke inflammatory response in tissue. In Zange et al., Journal of Controlled Release, 56, 1998, 249-258, the biocompatibility of various PEG-PLGA copolymers are examined with in vitro models, and none show adverse effects of the polymers on mouse fibroblasts. For a polymer to perform in a scaffold, good biocompatibility is not enough. The cells have to efficiently adhere to the material. It is known that PEG-containing polymers and PEG-coated surfaces resist adhesion of cells and proteins.
U.S. Pat. No. 6,201,072B1 teaches a group of PLGA-PEG-PLGA triblock copolymers with low molecular weight and distinct aqueous solubility characteristics for drug delivery applications.
WO 03000778 A1 uses (among other things) MPEG-PLGA (MPEG=methoxy-polyethylene glycol) with a linker in the OH-functional end for drug release purposes.
US 20040076673 discloses MPEG-PLGA with Mw<5000 for oral drug delivery.
CN 1446841 discloses three-dimensional porous frame materials of poly(lactide)-polyether block copolymers and a process for preparing such block copolymers.
The polymers for tissue engineering can be either natural or synthetic. The most widely used synthetic polymers are from the group of polyesters. The most common in this group are PLLA, PDLLA, PLGA, PCL (poly-ε-caprolactone), and various copolymers thereof. They are all hydrophobic materials, and initial adhesion of cells to scaffolds of these polyesters is sluggish at best.
The present inventors have found that by incorporating a hydrophilic block (i.e. a polyalkylene glycol block) in the polymer, the biocompatibility of polyesters is improved. This is due to better wetting characteristics of the material, and that initial cell adhesion is impaired on non-polar materials. Further, it has been found that by keeping the molar content of the polyalkylene units relative to the molar content of the lactide/glycolide units low, i.e. at the most 14 molar-%, superior polymers and derived materials are obtained.